The overall goal of this SBIR is the identification of small molecules that can reinforce the antitumor activity of DNA topoisomerase I inhibitors by acting at a biochemical locus linked functionally to topoisomerase I. This is to be done by selecting natural products from plant and marine extracts that inhibit the topoisomerase I-linked locus, and then modifying the structures of the isolated active principles. The compounds so identified will be evaluated in cell free systems, and in suitable yeast tester strains and mammalian cell lines. Optimized inhibitors will be evaluated in suitable animal tumor models as potentiators of the activity of DNA topoisomerase I inhibitors. PROPOSED COMMERCIAL APPLICATION: The goal of this program is the identification and commercialization of agents that can potentiate the activity of topisomerase I inhibitors as antitumor agents. The annual market for an agents. The annual market for an agent of this type should be well in excess of $100 million.